Structural and molecular basis of the assembly of the TRPP2/PKD1 complex

Mutations in PKD1 and TRPP2 account for nearly all cases of autosomal dominant polycystic kidney disease (ADPKD). These 2 proteins form a receptor/ion channel complex on the cell surface. Using a combination of biochemistry, crystallography, and a single-molecule method to determine the subunit composition of proteins in the plasma membrane of live cells, we find that this complex contains 3 TRPP2 and 1 PKD1. A newly identified coiled-coil domain in the C terminus of TRPP2 is critical for the formation of this complex. This coiled-coil domain forms a homotrimer, in both solution and crystal structure, and binds to a single coiled-coil domain in the C terminus of PKD1. Mutations that disrupt the TRPP2 coiled-coil domain trimer abolish the assembly of both the full-length TRPP2 trimer and the TRPP2/PKD1 complex and diminish the surface expression of both proteins. These results have significant implications for the assembly, regulation, and function of the TRPP2/PKD1 complex and the pathogenic mechanism of some ADPKD-producing mutations

Wigner Crystals Phases in Bilayer Quantum Hall Systems

(This is a substantially shortened version of the original abstract:) The Wigner crystal phase diagram of the bilayer systems have been studied using variational methods. Five crystal phases are obtained. As the layer spacing increases, the system will undergo a sequence of phase transitions. A common feature of most bilayer Wigner crystals is that they have mixed (pseudo-spin) ferromagnetic and antiferromagnetic order.Comment: 19 figures. Figures will be provided upon request. Submitted in PRB in Nov 94

Flexural behavior of UHPCbeam reinforced with steel-FRP composite bars

YesThis paper numerically investigates flexural performance of Ultra-High Performance Concrete (UHPC) beam reinforced with Steel-Fibre-Reinforced Polymer (FRP) Composite Bars (SFCBs) in terms of flexural stiffness, moment capacity, deflection, ductility and energy dissipation. The effect of various parameters, include the inner steel core area ratio of SFCB, yield strength of inner steel core, elastic modulus and ultimate strength of outer-wrapped FRP, reinforcement ratio, type and strength of concrete were studied. The results demonstrate that the inner steel core area ratio of SFCB, reinforcement ratio and the elastic modulus of SFCB's outer FRP have significant effect on the overall flexural performance of SFCB reinforced UHPC beam. The overall flexural performance of SFCB reinforced UHPC beam is slightly improved by increasing the yield strength of inner steel core of SFCB, but not affected by the ultimate strength of SFCB's outer FRP when specimen occurred compression failure. The results also exhibit that the flexural performance of UHPC beam reinforced with SFCBs is significantly improved when compared to those of reinforced high strength concrete (HSC) beam and normal strength concrete (NSC) beam. The flexural stiffness and the moment capacity of SFCB reinforced UHPC beam at the ultimate point were 2.0 and 2.4 times, respectively, of those of reinforced NSC counterpart.Natural Science Foundation of Jiangsu Province, China (BK20201436), the China Postdoctoral Science Foundation (2018M642335), the Science and Technology Project of Jiangsu Construction System, China (2018ZD047, 2021ZD06), the Science and Technology Project of Gansu Construction System, China (JK2021-19), the National Natural Science Foundation of China (51678514), the Science and Technology Innovation Fund of Yangzhou University, China (2020-65), the Open Foundation of Jiangsu Province Engineering Research Center of Prefabricated Building and Intelligent Construction, China (2021), the Science and Technology Cooperation Fund Project of Yangzhou City and Yangzhou University, China (YZU212105), the Practice and Innovation Plan for Postgraduates in Jiangsu Province, China (SJCX21_1589), the Blue Project Youth Academic Leader of Colleges and Universities in Jiangsu Province, China (2020) and the Deputy General Manager Science and Technology Project of Jiangsu Province, China (FZ20200869). Reference

ROP: dumpster diving in RNA-sequencing to find the source of 1 trillion reads across diverse adult human tissues.

High-throughput RNA-sequencing (RNA-seq) technologies provide an unprecedented opportunity to explore the individual transcriptome. Unmapped reads are a large and often overlooked output of standard RNA-seq analyses. Here, we present Read Origin Protocol (ROP), a tool for discovering the source of all reads originating from complex RNA molecules. We apply ROP to samples across 2630 individuals from 54 diverse human tissues. Our approach can account for 99.9% of 1 trillion reads of various read length. Additionally, we use ROP to investigate the functional mechanisms underlying connections between the immune system, microbiome, and disease. ROP is freely available at https://github.com/smangul1/rop/wiki

No major flaws in "Identification of individuals by trait prediction using whole-genome sequencing data"

In a recently published PNAS article, we studied the identifiability of genomic samples using machine learning methods [Lippert et al., 2017]. In a response, Erlich [2017] argued that our work contained major flaws. The main technical critique of Erlich [2017] builds on a simulation experiment that shows that our proposed algorithm, which uses only a genomic sample for identification, performed no better than a strategy that uses demographic variables. Below, we show why this comparison is misleading and provide a detailed discussion of the key critical points in our analyses that have been brought up in Erlich [2017] and in the media. Further, not only faces may be derived from DNA, but a wide range of phenotypes and demographic variables. In this light, the main contribution of Lippert et al. [2017] is an algorithm that identifies genomes of individuals by combining multiple DNA-based predictive models for a myriad of traits

JWST MIRI/Medium Resolution Spectrograph (MRS) observations and spectral models of the underluminous yype Ia supernova 2022xkq

We present a JWST mid-infrared (MIR) spectrum of the underluminous Type Ia Supernova (SN Ia) 2022xkq, obtained with the medium-resolution spectrometer on the Mid-Infrared Instrument (MIRI) ∼130 days post-explosion. We identify the first MIR lines beyond 14 μm in SN Ia observations. We find features unique to underluminous SNe Ia, including the following: isolated emission of stable Ni, strong blends of [Ti ii], and large ratios of singly ionized to doubly ionized species in both [Ar] and [Co]. Comparisons to normal-luminosity SNe Ia spectra at similar phases show a tentative trend between the width of the [Co iii] 11.888 μm feature and the SN light-curve shape. Using non-LTE-multi-dimensional radiation hydro simulations and the observed electron capture elements, we constrain the mass of the exploding WD. The best-fitting model shows that SN 2022xkq is consistent with an off-center delayed-detonation explosion of a near-Chandrasekhar mass WD (MWD ≈1.37 M⊙) of high central density (ρc ≥ 2.0 × 109 g cm−3) seen equator-on, which produced M(56Ni) =0.324 M⊙ and M(58Ni) ≥0.06 M⊙. The observed line widths are consistent with the overall abundance distribution; and the narrow stable Ni lines indicate little to no mixing in the central regions, favoring central ignition of subsonic carbon burning followed by an off-center deflagration-to-detonation transition beginning at a single point. Additional observations may further constrain the physics revealing the presence of additional species including Cr and Mn. Our work demonstrates the power of using the full coverage of MIRI in combination with detailed modeling to elucidate the physics of SNe Ia at a level not previousl